rs17202296

Positions:

• chr16-81925586-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002661.5(PLCG2):​c.2418-1496G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,150 control chromosomes in the GnomAD database, including 4,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4584 hom., cov: 32)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

PLCG2 (HGNC:9066): (phospholipase C gamma 2) The protein encoded by this gene is a transmembrane signaling enzyme that catalyzes the conversion of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1D-myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) using calcium as a cofactor. IP3 and DAG are second messenger molecules important for transmitting signals from growth factor receptors and immune system receptors across the cell membrane. Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCG2	NM_002661.5	c.2418-1496G>C		intron_variant		ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6	c.2418-1496G>C		intron_variant		1	NM_002661.5	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37058 AN: 152032 Hom.: 4582 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37077 AN: 152150 Hom.: 4584 Cov.: 32 AF XY: 0.241 AC XY: 17896 AN XY: 74394

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.247

Alfa AF: 0.101 Hom.: 171

Bravo AF: 0.236

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17202296; hg19: chr16-81959191;